Multiple sclerosis (MS) is an inflammatory demyelinating disease of the human central nervous system of unknown etiology and pathogenesis. Although an autoimmune basis for the pathogenesis of MS is suspected, the putative antigen(s) responsible for initiating demyelination in MS is unknown despite many years of intensive research. Recently it has been demonstrated that glycolipids and glycoproteins are important antigens in a large proportion of patients with the demyelinating neuropathy associated with monoclonal IgM gammopathy and with the Guillain-Barre' syndrome. We hypothesize that autoantibodies to complex glycolipids and proteins may also be present in MS, and may play a role in the pathogenesis of MS. We propose to systematically test sera and cerebrospinal fluid from a large number of patients with MS and controls, for the presence of autoantibodies to complex glycolipid and protein antigens. To do this, we will use three sensitive methods: immunoblots, enzyme-linked immunosorbent assay (ELISA), and a thin-layer chromatogram- immunostaining technique. We will attempt to determine the relationship of autoantibody titer to clinical disease course by examining serial serum specimens from MS patients with relapsing-remitting, clinically stable, relapsing progressive and chronic progressive MS patients. Identifying the antigen may provide invaluable information for establishing the pathogenesis, and could lead to the development of better therapies.